ABSTRACT HIV disproportionately affects young women, and nearly 200,000 young women in sub-Saharan Africa are infected with HIV each year. Pre-exposure prophylaxis (PrEP) is an effective method for preventing HIV infection and offers promise as a female-controlled intervention. However, effective strategies for efficiently identifying women at high risk of HIV infection and engaging them in PrEP have not been established. Pregnant and postpartum women have elevated risk of HIV infection, and HIV infection acquired during pregnancy can be transmitted to infants perinatally or during breastfeeding. Therefore, integrating PrEP into existing maternal and child health (MCH) clinics could be an efficient strategy for preventing new HIV infections. National health programs operating under limited resources need guidance to determine where to roll out PrEP to maximize impact. The proposed project will use mathematical modeling combined with data from two implementation studies to evaluate the cost-effectiveness of PrEP delivery through MCH clinics in western Kenya. In Aim 1, we will conduct a microcosting study as part of a PrEP demonstration project to estimate the incremental cost of integrating PrEP into routine MCH services. In Aim 2, we will develop an individual-based mathematical model of HIV transmission calibrated to HIV dynamics in western Kenya that simulates HIV natural history, demography, sexual relationship formation, and explicitly models the flow of individuals through HIV and MCH services. Using this model, we will evaluate the population-level impact of PrEP uptake by pregnant and postpartum women attending MCH clinics. Combined with the cost estimates from Aim 1, we will calculate the cost-effectiveness and budget impact of this PrEP delivery strategy compared to standard thresholds and other HIV prevention interventions. A key benchmark of program success is the extent to which PrEP use is prioritized among individuals with high HIV risk. In Aim 3, we will estimate the cost-effectiveness of risk score-guided vs. universal PrEP delivery to pregnant women. This analysis will incorporate results from a randomized trial comparing PrEP uptake, retention, and adherence between the two strategies into the model developed in Aim 2. Together, the results from these Aims will help guide policymakers decide how to most effectively scale up PrEP delivery in sub-Saharan Africa. In addition to these Aims, the proposal describes a rigorous training plan in mathematical modeling, health economics, and clinical care as well as mentorship from leading HIV prevention researchers. Combined, this proposal will provide a solid foundation for a career as an infectious disease clinician and public health researcher contributing to efforts to control the HIV epidemic.